Rhinosinusitis prevention and therapy with proinflammatory cytokine inhibitors

Abstract

The invention describes a method of treating upper airway disease by administering a composition of one or more proinflammatory cytokine inhibitors sufficient to inhibit inflammation in the upper airways. The proinflammatory cytokines that are inhibited include TNF, IL-1 and IL-8. A medication dispensing unit which includes a container and a delivery system is used to administer the composition. The delivery system further encompasses a one-way valve, a microcatheter, or a liquid-pressure type sprayer.

Description

RELATED APPLICATION[0001]This application claims the benefit of U.S. Provisional Application 60 / 819,703 (filed Jul. 11, 2006), U.S. Provisional Application 60 / 878,397 (filed Jan. 4, 2007), and U.S. Provisional Application 60 / 907,027 (filed Mar. 16, 2007), all of which are incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to methods for treating a disease of the upper airways with proinflammatory cytokine inhibitors.BACKGROUND OF THE INVENTION[0003]Upper airways disease or rhinosinusitis are common disorders with over 33 million cases annually in the US. Both acute and chronic forms of sinusitis are common leading to over 12 million physician visits annually. Of rhinosinusitis sufferers, up to 500,000 people resort to sinus surgery in the U.S. each year. A recent epidemiological review (Vital Health Statistics, USA, 10:1999) ranks chronic rhinosinusitis as the most common chronic condition in the U.S. affecting more people than hype...

AI Technical Summary

Benefits of technology

[0021]The invention provides for glycols, glycerin, proinflammatory cytokine inhibitor, pharmaceutically acceptable carrier, and a delivery device capable of expressly delivering said compositions to the upper airways. The compositions may contain a single active ingredient such as a proinflammatory cytokine inhibitor that may be administered to the mammal in need of treatment, or alternatively, may contain one or more additional pharmacologic agents capable of reducing inflammation, secretions, infection, pain, or hydrating secretions. The invention also provides methods for formulating a composition containing a proinflammatory cytokine inhibitor with an effective amount of one or more pharmacologic agents such as e.g., anti-inflammatory agents, antibiotics, antifungals, antivirals, steroids, pain relievers, surfactants, hydrating agents, vaccines, and other pharmacologically active and inactive compounds.

[0022]The method of treating upper airway disease, in accord with the invention, comprises administering a therapeutically effective amount of a composition comprising one or more inflammatory cytokine inhibitors. In one embodiment, the inhibited proinflammatory cytokine is TNF, IL-1, or IL-8. The proinflammatory cytokine inhibitor composition is administered in an amount sufficient to inhibit inflammation in the upper airways. Advantageously, a therapeutically or prophylactically effective amount of the composition is typically in the range of 0.1 mg to 100 mg daily, administered in single or divided doses. The composition may be administered in spray, aerosol, gel, solution, emulsion or suspension form. As another aspect, the method of administration of the composition may be perioral, intranasal, topical, or parenteral. The composition may be applied directly to the upper airways or the paranasal sinuses via microcatheter.

Problems solved by technology

The sinuses communicate with the rest of the upper airways through small orifices or ostium that may become obstructed leading to symptoms and disease.

These sites are difficult to reach with aerosols or systemic bioactive substances, as compared to other tissues.

Larger systemic doses are required to deliver therapeutically effective amounts of bioactive agents to the upper airways, which increase the likelihood of adverse events.

Moreover, inadequate dosing can lead to microbial resistance, spread of disease, and continued suffering of the subject.

Polyps are benign masses of extra tissue that cause problems related to their size and location.

Nasal and sinus polyps form commonly in severe or chronic disease and can obstruct drainage of the nose and sinuses, and in extreme instances, may even protrude from the nose.

For most subjects with nasal polyps, treatment consists of both medical and surgical management, as surgery cannot treat the underlying inflammatory component of the mucosal disease.

While antibiotics are useful in treating the acute exacerbations of rhinosinusitis, antibiotics alone often do not eliminate the underlying often-chronic inflammation.

Moreover, systemic antibiotics are often less effective because of poor tissue penetration associated with rhinosinusitis.

Intranasal and oral corticosteroids, have been used extensively to reduce the inflammation that plays a critical role in rhinosinusitis, but corticosteroids can cause serious side effects including thinning of membranes, bleeding, growth retardation in children, and osteoporosis; and when possible must be avoided or cautiously used with patients that have certain conditions, such as gastrointestinal ulcers, renal disease, hypertension, diabetes, osteoporosis, thyroid disorders, and intestinal disease.

It may also decrease blood flow resulting in decongestion, and infectious organisms are also removed with the nasal secretions.

Despite these reports, rehydrating and flushing agents do not treat the underlying inflammation in rhinosinusitis and other problems including pain, infection, viscous secretions, and polyps.

No convincing data exists to support the use of antihistamines and decongestants in rhinosinusitis.

The utility of nucleases in rhinosinusitis is limited however because these agents do not decrease inflammation and nor do they treat the underlying etiologic agent.

Surgeries frequently used in rhinosinusitis to improve sinus drainage are rooted in the theory that the disease can be reversed by identifying and correcting the obstruction that caused the condition, but while such surgery usually offers temporary relief of symptoms, it is typically not curative.

Polyps are benign masses of extra tissue that cause problems related to their size and location.

Nasal and sinus polyps form commonly in CF and can obstruct drainage of the nose and sinuses, and in extreme instances, may even protrude from the nostrils.

In addition, sinus surgery without aggressive follow-up medical care, such as upper airway clearance measures or inhaled corticosteroids, is not useful (Mak et al.

Another major current limitation in treating rhinosinusitis is the inability to achieve sufficient drug levels in these inflamed tissues.

While a variety of catheters, microcatheters and cannulae are used in procedures to deliver fluid, gas, suction and energy to select regions of the body, none have been employed effectively in treating rhinosinusitis.